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Genotype FBN1 /phenotype relationship in a cohort of patients with Marfan syndrome
Author(s) -
Hernándiz Amparo,
Zúñiga Angel,
Valera Francisco,
Domingo Diana,
OntoriaOviedo Imelda,
Marí Jose F.,
Román Jose A.,
Calvo Inmaculada,
Insa Beatriz,
Gómez Rosa,
Cervera José V.,
Miralles Manuel,
Montero Jose A.,
MartínezDolz Luis,
Sepúlveda Pilar
Publication year - 2021
Publication title -
clinical genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.543
H-Index - 102
eISSN - 1399-0004
pISSN - 0009-9163
DOI - 10.1111/cge.13879
Subject(s) - marfan syndrome , haploinsufficiency , genotype , fibrillin , aortic dissection , ectopia lentis , phenotype , medicine , connective tissue disease , genetics , cohort , gene , biology , pathology , aorta , disease , autoimmune disease
Abstract Marfan syndrome (MFS) is a systemic connective tissue disorder caused by mutations in the fibrillin‐1 ( FBN1 ) gene, and cardiovascular involvement is the leading cause of mortality. We sought to examine the genotype/phenotype realtionship in 61 consecutive patients with a phenotype and genotype compatible with MFS. The FBN1 gene was analyzed by massive sequencing using a hybridization capture‐based target enrichment custom panel. Forty‐three different variants of FBN1 were identified, of which 17 have not been previously reported. The causal variants of MFS were grouped into mutations resulting in haploinsufficiency (HI group; 23 patients) and mutations producing a dominant‐negative effect (DN group; 38 patients). Patient information was collected from electronic medical records and clinical evaluation. While no significant differences were found between the two groups, the HI group included more cases with aortic dissection and occurring at a younger age that the DN group (34.7% vs. 15.8%; p = 0.160). Irrespective of the mutation group, males presented with a higher probability of aortic involvement (4‐fold higher risk than females) and aortic dissections events occurred at younger ages. Patients with DN variants carrying a cysteine substitution had a higher incidence of ectopia lentis .